Studies in several tissues have demonstrated CF (cystic fibrosis)-related abnormalities in autonomic regulation of tissue function. Among these are an increased sensitivity to cholinergic agents and a decreased sensitivity to beta-adrenergic agents. If CF mucous glands also have increased sensitivity to cholinergic agonists, then the resulting increased mucus secretion might contribute to the bronchial pathophysiology observed in these patients. However, a previous study (Mangos, J Dent Res 60, 797, 1981) utilizing a serous human salivary gland--the parotid--came to just the opposite conclusion with regard to CF-related abnormalities in autonomic control. Hence, it is important to determine how the regulation of human mucous salivary gland function is affected in CF. This proposal utilizes measurements of stimulation induced changes in intracellular elemental concentrations to test for CF-related changes in sensitivity to parasympathomimetic and sympathomimetic agents. Elemental concentrations in different intracellular organelles in human labial glands incubated in vitro under different experimental conditions will be measured using X-ray microanalysis. Temporal and spatial concentration dependencies following gland stimulation with cholinergic and adrenergic agonists will be analyzed using appropriate coding and computer assisted analysis of variance techniques. Spatial dependencies will also be analyzed using digital imaging techniques. The in vitro results will not only allow statistical tests for altered sensitivities to cholinergic and adrenergic agonists, but also for disease related changes in resting intracellular elemental concentrations as previously reported for the parotid gland. Moreover, the present study will extend previous findings by allowing a determination of the intracellular organelles in which the concentration changes occur. In addition, use of Co-EDTA will provide an objective method for detecting cells injured in the preparatory procedure, and the use of the variable osmols (defined as the sum of Na + K + C1) will allow an estimation of disease and stimulation related changes in osmotic driving forces. Most importantly, the use of human labial gland tissues obtained by biopsy from patients with CF will maximize the likelihood that the results will be relevant to CF.